This invention relates to novel compositions comprising ethylene oxide and pentafluorodimethyl ether which possess improved environmental and nonflammability characteristics. These compositions are useful in the gaseous sterilization of heat and/or moisture sensitive materials.
Sterilization with a germicidal agent, such as ethylene oxide gas or ethylene oxide containing gas mixtures, has played an increasingly important role in sterilizing heat or moisture sensitive materials. Rapid growth in the use of sterile, disposable medical devices is just one consequence of gaseous sterilization with agents such as ethylene oxide. Gaseous sterilization of reusable medical and surgical equipment using a nonflammable mixture of ethylene oxide and a carrier gas has also proven to be reliable, cost effective technology for many hospitals.
The basic gaseous sterilization process consists of evacuating the sterilization chamber containing the articles to be sterilized, preconditioning the articles at an optimal relative humidity, generally between 20-70% relative humidity, admitting the sterilizing gas at an appropriate pressure and temperature, maintaining contact between the sterilizing atmosphere and the articles to be sterilized for an appropriate time, and finally discharging and evacuating the chamber to remove the sterilant gas.
Although there are many variations on the basic process, the major factors which have to be controlled in order to effect the sterilization are exposure time, temperature, ethylene oxide pressure or partial pressure, and relative humidity. The following prior art references provide a good description of the standard sterilization processes and apparatus with which the gaseous sterilizing agents of the invention are useful: J. J. Perkins, Principles and Methods of Sterilization 2nd. Ed. 501-530 (1969) and "Ethylene Oxide Gaseous Sterilization For Industrial Applications" Industrial Sterilization International Symposium, 181-208 (1972), U.S. Pat. No. 3,068,064 and U.S. Pat. No. 3,589,861.
By itself, ethylene oxide is an extremely flammable gas. Its flammability range extends from about 3.0% by volume to 100% by volume in air. Thus, when ethylene oxide is used alone as a sterilizing gas, precautions such as explosion proof equipment are mandatory.
A preferable practice is to blend the ethylene oxide with another fluid which serves to dilute the ethylene oxide and render the mixture as a whole, nonflammable. Two such blends which have been used as sterilizing gases are dichlorodifluoromethane (chlorofluorocarbon (CFC)-12)/ethylene oxide and carbon dioxide/ethylene oxide. Inert carrier gases like CFC-12 and carbon dioxide inhibit the flammability of ethylene oxide and provide sufficient autogeneous pressure to deliver the liquid mixture from the source cylinder to the heat exchanger of the sterilizer vessel where the liquid mixture is vaporized.
The CFC-12/ethylene oxide blend is generally supplied as a liquid mixture consisting of 88% by weight CFC-12 and 12% by weight ethylene oxide. This composition is below the critical flammability composition of about 14-15% by weight ethylene oxide in CFC-12, and is therefore nonflammable. A typical hospital sterilization process which utilizes the CFC-12/ethylene oxide blend is performed by evacuating the chamber to about 20-24 inches of mercury vacuum, preconditioning the articles at an optimal relative humidity, and filling the chamber to about 10 psig pressure with the gas mixture. Sterilization is generally performed around 130.degree. F. The 88/12 by weight CFC-12/ethylene oxide mixture produces a gas mixture containing 72.8 volume or mole percent CFC-12 and 27.2 volume or mole percent ethylene oxide. This composition provides about 630 milligrams of ethylene oxide per liter at the stated typical operating condition. The concentration (mg/liter) of ethylene oxide present in the sterilization chamber is critical in determining the required exposure time and ultimate sterilization efficiency. The Association for the Advancement of Medical Instrumentation (AAMI) recommends a minimum ethylene oxide concentration of 400 mg/liter.
The nonflammable carbon dioxide/ethylene oxide blend is also supplied as a liquid mixture consisting of about 90% by weight carbon dioxide and about 10% by weight ethylene oxide. This blend produces a gas mixture containing 90% by volume or mole carbon dioxide and 10% by volume or mole ethylene oxide. The available ethylene oxide concentration (mole percent) is significantly less than that obtained from the 88/12 by weight CFC-12/ethylene oxide blend. Sterilization using carbon dioxide/ethylene oxide is generally performed at a greater pressure than that used with CFC-12/ethylene oxide to increase the concentration of ethylene oxide, or is performed for greater exposure times which decreases productivity.
Although the major purpose of the inert carrier gas component in these sterilizing gas mixtures is to mask the flammability characteristics of ethylene oxide, simple substitution of an arbitrary nonflammable gas does not necessarily ensure a useful sterilizing gas mixture. First, the flammability properties of the blend must be such that sufficient ethylene oxide (mg/liter at a typical pressure and temperature) is delivered by the blend to effect the sterilization in an appropriate time. If the carrier gas does not mask the flammability to a sufficient extent, a lower concentration of ethylene oxide must be used to ensure nonflammability. In such cases, either a longer exposure time is required to perform the sterilization, which affects productivity, or greater operating pressures are required to increase the effective ethylene oxide density in the sterilization chamber. Increasing the operating pressure is generally not a viable option because existing sterilization chambers may not be rated for the increased pressure, and as pointed out by Gunther in U.S. Pat. No. 3,589,861, increased pressure can lead to swelling and rupture of the sealed plastic bags commonly used to package disposable medical devices. Indeed, lower operating pressures are advantageous in this respect. The requirement for a greater operating pressure or increased exposure time has limited the acceptance of the 90/10 carbon dioxide/ethylene oxide mixture in comparison to the 88/12 CFC-12/ethylene oxide mixture.
A candidate inert diluent or carrier gas must also be miscible with ethylene oxide in the liquid phase and must not segregate from the ethylene oxide to any great extent during vaporization. Segregation or fractionation can lead to potentially flammable or explosive situations. The degree of segregation that may occur during evaporation is related to the relative volatility of the components of the mixture. The vapor pressure of ethylene oxide at 70.degree. F. is 22 psia while the vapor pressures of CFC-12 and carbon dioxide at 70.degree. F. are 85 and 850 psia, respectively. The vapor pressure data indicate a very large difference in volatility between carbon dioxide and ethylene oxide and, hence, a susceptibility for carbon dioxide/ethylene oxide blends to fractionate.
Because CFC's like the fully halogenated CFC-12 have been implicated in causing environmental problems such as stratospheric ozone depletion and global warming they are not preferred diluents. The trend in the industry is toward the use of stratospherically safer (i.e. hydrogen containing) materials as the flame suppressing diluent. Hydrochlorofluorocarbon (HCFC)-based diluents such as 1-chloro-1,2,2,2-tetrafluoroethane (HCFC-124) and a blend of chlorodifluoromethane (HCFC-22)/HCFC-124 are currently being used. These materials are available from AlliedSignal Inc. of Morristown, N.J. Even though these materials possess significant environmental advantages over perhalogens (lower ozone depletion potentials), because they contain some chlorine they are viewed as temporary solutions with limited lives.
Materials such as the hydrofluorocarbons or HFC's, which contain fluorine, hydrogen and no chlorine, are more acceptable. Examples of these materials are HFC-125 and HFC-227. They have zero or essentially zero ozone depletion potentials and atmospheric lifetimes of substantially less than the CFC's. Other materials that contain fluorine, hydrogen but no chlorine such as ethers are also candidate diluents. Pentafluorodimethyl ether is one such compound. It is essentially non-ozone depleting and has an atmospheric lifetime of about 17 years, which is significantly lower than that of most CFC's (CFC-12/116 year lifetime)